The physiological actions of prostaglandin (PG)E.sub.2 are mediated through interaction with the prostaglandin E receptor(s). There are three subtypes of the EP receptor, EP.sub.1, EP2 and EP.sub.3 (for review see Coleman et al., 1989). These three subtypes all show high affinity for PGE2 but show differences in their affinities for various agonists and antagonists and exert their actions through different secondary transduction mechanisms. Thus activation of the EP1 receptor is associated with a rise in IP3 and intracellular calcium, activation of the EP2 receptor results in a rise in intracellular cyclic AMP and activation of the EP3 receptor a fall in intracellular cyclic AMP. To date the only members of this family to be cloned are the mouse EP2 (Honda et al., 1993) and the mouse EP.sub.3.alpha. and EP.sub.3.beta. (Sugimoto et al., 1992; Sugimoto et al., 1993) subtypes. EP2 receptors are normally found on a wide variety of cells including the small intestine, kidney, stomach, muscle, eye, uterus, thymus and trachea, in humans and other animals. Binding of prostaglandin E.sub.2 to the EP2 receptor protein elicits an increase in intracellular cAMP levels. This signal causes the tissues to respond, for example, by smooth muscle relaxation.
Functional activities of the EP2 receptor have been studied using tissue preparations such as guinea-pig ileum circular muscle, cat trachea, guinea-pig trachea and cell preparations, such as lymphocytes and osteoclasts. The above methods for studying EP2 receptor activities have several disadvantages in that they require preparations containing several different but related receptor populations, with different ligand binding properties making measurements of absolute potency and selectivity very difficult. In addition, tissues contain very low levels of EP2 receptor and since tissue samples are required, compounds cannot satisfactorily be tested as effectors of the human EP2 receptor.